Pantoprazole

2.05

log Kow = 2.2 /Estimated/

Freely soluble in water.

In water, 48 mg/L at 25 °C /Estimated/

149-150

139-140 °C, decomposes

Mol wt: 405.36. White to off-white solid; mp: >130 °C (dec); UV max (methanol): 289 (E=1.64X10+4) /Sodium salt/

3.92 and 8.19

pKa1 = 3.92, pKa2 = 8.19

185.5 Ų [M+Na]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID7044215]；185.5 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: APCI+; Dataset: TOXCAST; Source Identifier: DTXSID7044215]；185.2 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID7044215]；187.0 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID7044215]

190.01 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；177.08 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；182 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；184.56 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

183.4 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

184.38 Ų [M+H]+；188.02 Ų [M-H]-；184.94 Ų [M+Na]+

Freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in hexane. /Sodium/

White to off-white crystalline powder and is racemic /Sodium sesquihydrate/

Hydroxyl radical reaction rate constant = 1.0X10-14 cu cm/molc-sec at 25 °C /Estimated/

Warning

H302+H312+H332 (20%): Harmful if swallowed, in contact with skin or if inhaled [Warning Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]；H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]；H312 (20%): Harmful in contact with skin [Warning Acute toxicity, dermal]；H315 (50%): Causes skin irritation [Warning Skin corrosion/irritation]；H319 (40%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H332 (20%): Harmful if inhaled [Warning Acute toxicity, inhalation]；H335 (40%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]；H336 (10%): May cause drowsiness or dizziness [Warning Specific target organ toxicity, single exposure; Narcotic effects]；H341 (10%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]；H351 (10%): Suspected of causing cancer [Warning Carcinogenicity]；H400 (10%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410 (10%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]；H412 (10%): Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P203, P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 10 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl pantoprazole sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Pantoprazole Sodium/

Der G; An Overview of Proton Pump Inhibitors; Gastroenterol Nurs 26 (5): 182-90 (2003)

Poole P; Pantoprazole; Am J Health Syst Pharm 58 (11): 999-1008 (2001). The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of pantoprazole are reviewed.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Pantoprazole causes prolonged inhibition of gastric acid secretion, and thereby may interfere with the absorption of these medications /ampicillin or iron salts or ketoconazole/ and others for which bioavailability is determined by gastric pH. /Pantoprazole sodium/

Pantoprazole, although metabolized by hepatic cytochrome p450 systems, does not appear to either inhibit or induce cytochrome p450 enzyme activity. To date, no clinically significant interactions have been noted from such commonly used drugs as diazepam, phenytoin, nifedipine, theophylline, digoxin, warfarin, or oral contraceptives. /Pantoprazole sodium/

Pantoprazole, by increasing gastric pH, has the potential to affect the bioavailability of any medication for which absorption is pH-dependent. Also, pantoprazole may prevent the degradation of acid-labile drugs. /Pantoprazole sodium/

In other in vivo studies, ethanol, glyburide, caffeine, antipyrine, metronidazole, and amoxicillin, had no clinically relevant interactions with pantoprazole. /Pantoprazole sodium/

Despite its wide use, pantoprazole has only rarely been associated with hepatic injury. In large scale, long term trials of pantoprazole, serum ALT elevations have occurred in less than 1% of patients and at rates similar to those that occur with placebo or comparator drugs. Only a small number of cases of clinically apparent liver disease attributed to pantoprazole have been published, but the clinical pattern of injury has resembled acute hepatic necrosis which has been described with other proton pump inhibitors. Clinically apparent liver injury due to proton pump inhibitors generally arises within the first 4 weeks of therapy and is characterized by an acute hepatocellular pattern of injury with rapid recovery upon withdrawal. Rash, fever and eosinophilia are rare, as is autoantibody formation. In large case series of drug induced liver injury, pantoprazole has accounted for few instances of symptomatic acute liver injury.；Likelihood score: C (probable rare cause of clinically apparent liver injury).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 13,000(SRC), determined from a structure estimation method(2), indicates that pantoprazole is expected to be immobile in soil(SRC). The pKa1 and pKa2 of pantoprazole are 3.92 and 8.19(3), respectively, indicating that this compound will primarily exist in the protonated form in the environment and cations generally adsorb to organic carbon and clay more strongly than their neutral counterparts(4). Volatilization of pantoprazole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.84X10-20 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Pantoprazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.25X10-12 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation of pantoprazole in soil is unknown(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 13,000(SRC), determined from a structure estimation method(2), indicates that pantoprazole is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.84X10-20 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). The pKa1 and pKa2 of pantoprazole are 3.92 and 8.19(5), respectively, indicating that this compound will primarily exist in the protonated form in the environment; cations generally adsorb more strongly to suspended solids and sediment than their neutral counterparts(6). According to a classification scheme(7), an estimated BCF of 10.3(SRC), from an estimated log Kow of 2.22(8) and a regression-derived equation(9), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Biodegradation of pantoprazole in water is unknown(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), pantoprazole, which has a an estimated vapor pressure of 1.25X10-12 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase pantoprazole may be removed from the air by wet and dry deposition(SRC).

Even though pantoprazole is a relatively benign medication, there is still a risk of adverse effects. The primary adverse effects of pantoprazole include diarrhea, headache, upper respiratory tract infection, and abdominal pain. Long-term complications of pantoprazole use include diarrhea attributed to Clostridium difficile or microscopic colitis, small-intestinal bacterial overgrowth, vitamin B12 deficiency, iron deficiency, calcium deficiency, magnesium deficiency, bone demineralization, interstitial nephritis, and diminished absorption of medications such as clopidogrel. There is a rare risk of subacute cutaneous lupus erythematosus associated with pantoprazole administration, and Health Canada acknowledged this risk in December 2017. In older adults specifically, treatment with pantoprazole for 8 weeks or longer is not recommended. The Beers Criteria classifies pantoprazole as an inappropriate medication for the older population due to an associated increased risk of Clostridium difficile infection and bone density loss. A recent study has reported that QTc prolongation in critically ill patients; additional research is required.；Drug-Drug Interactions；* :；* Rilpivirine: Concomitant use is contraindicated due to decreased antiviral effect and risk of drug resistance.；* Atazanavir: Monitor for potential reduced efficacy; consult dosing recommendations for adjustments.；* Nelfinavir: Avoid concomitant use due to decreased efficacy.；* :According to product labeling, altered INR and prothrombin time are possible. Regular monitoring of INR is required, and warfarin dose adjustments may be necessary. However, one study suggests conflicting results.；* : Pantoprazole can lower gastric acidity, reducing the absorption of drugs such as iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, and ketoconazole/itraconazole. Monitoring and possible dose adjustments may be necessary to maintain the effectiveness.；* : Concomitant use, especially at high doses, may increase and prolong serum methotrexate levels, potentially causing toxicity.；* Incompatibility: Midazolam IV is incompatible with Y-site administration of IV pantoprazole.；Drug-Laboratory Interactions；* Tetrahydrocannabinol levels: There have been instances of false-positive results in urine screenings for tetrahydrocannabinol in patients taking proton pump inhibitors (PPIs), including pantoprazole. Clinicians should interpret these results with caution.；* Neuroendocrine tumor diagnostics: Proton pump inhibitor–induced acid suppression can elevate serum chromogranin A (CgA) concentrations, potentially leading to false-positive interpretations during neuroendocrine tumor diagnostics. Discontinuation of pantoprazole for at least 14 days before CgA measurement is recommended; retesting should be considered if levels remain elevated. Consistent use of the same assay laboratory is advised for serial assessments due to inter-assay variability in the reference range.

Signs and Symptoms of Overdose；There have not been a significant number of pantoprazole overdoses that have resulted in serious medical consequences. Laboratory studies have shown that single doses ranging from 709 to 887 mg/kg caused death in animal subjects (mice, rats, and dogs). Acutely, evidence of hypoactivity, tremor, and ataxia was observed in these animals.；Management of Overdose；There is no specific antidote for an event such as this. Furthermore, pantoprazole is not removable from the body via hemodialysis. As a result, treatment for pantoprazole overdose focuses on symptomatic relief. Contact the poison control center (800-222-1222) for the most up-to-date recommendations.

Using a structure estimation method based on molecular connectivity indices(1), the Koc for pantoprazole can be estimated to be 13,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that pantoprazole is expected to be immobile in soil. The pKa1 and pKa2 of pantoprazole are 3.92 and 8.19(3), respectively, indicating that this compound will primarily exist in the protonated form in the environment. Cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(4).

/SIGNS AND SYMPTOMS/ Anaphylaxis has been reported with the use of IV pantoprazole sodium. Immediate medical intervention and drug discontinuance are required if anaphylaxis or other severe hypersensitivity reactions occurs. /Pantoprazole sodium/

/CASE REPORTS/ There have been spontaneous reports of overdosage with pantoprazole, including a suicide in which pantoprazole 560 mg and undetermined amounts of chloroquine and zopiclone were also ingested. There have also been spontaneous reports of patients taking similar amounts of pantoprazole (400 and 600 mg) with no adverse effects. /Pantoprazole sodium/

/CASE REPORTS/ A 61 -year-old man took one tablet of pantoprazole 40 mg one year after first being treated with the drug. Within hours after ingestion, he developed malaise, generalized pruritus and urticaria, a swollen tongue and eyes, and diffuse sweating; his blood pressure decreased to 75/50 mm Hg. Because of the acute onset of symptoms and close temporal association with exposure to the drug, as well as previous exposure to it, the reactions can be classified as anaphylactic shock to PPIs. /Pantoprazole sodium/

/CASE REPORTS/ A case of acute interstitial nephritis, which developed after 6 weeks of treatment with pantoprazole /was reported/. A 23-year-old man presented with acute renal failure requiring renal replacement therapy. Acute interstitial nephritis was diagnosed by renal biopsy and was successfully treated with corticosteroids and withdrawal of pantoprazole. /Pantoprazole sodium/

/CASE REPORTS/ A 46-year-old woman presented for an emergency admission because of colic-like upper abdominal pain and markedly impaired general condition. Eight days before admission she had started and continued to take pantoprazole because of symptoms of gastroesophageal reflux. Clinical examination and laboratory tests indicated abnormal liver functions suggesting hepatitis. Serology largely excluded an infectious, autoimmunological or metabolic cause. Duplex sonography gave no evidence of bile obstruction or Budd-Chiari syndrome. The patient's condition and laboratory tests after the drug had been discontinued gradually improved on symptomatic treatment, indicating pantoprazole-induced hepatitis. Intake of proton pump inhibitors is a rare cause but should be considered in the differential diagnosis of hepatitis of uncertain etiology. /Pantoprazole sodium/

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

pantoprazole

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

An estimated BCF of 10.3 was calculated for pantoprazole(SRC), using an estimated log Kow of 2.22(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for pantoprazole is estimated as 5.84X10-20 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that pantoprazole is expected to be essentially nonvolatile from water surfaces(2). The pKa1 and pKa2 of pantoprazole are 3.92 and 8.19(3), respectively, indicating that this compound will primarily exist in the protonated form in the environment therefore volatilization from moist soil and water surfaces are not expected to be an important fate process. Pantoprazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure 1.25X10-12 mm Hg(SRC), determined from a fragment constant method(4).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl pantoprazole sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Pantoprazole Sodium/

A02BC02

A - Alimentary tract and metabolism；A02 - Drugs for acid related disorders；A02B - Drugs for peptic ulcer and gastro-oesophageal reflux disease (gord)；A02BC - Proton pump inhibitors；A02BC02 - Pantoprazole

QA - Alimentary tract and metabolism；QA02 - Drugs for acid related disorders；QA02B - Drugs for peptic ulcer and gastro-oesophageal reflux disease (gord)；QA02BC - Proton pump inhibitors；QA02BC02 - Pantoprazole

This drug acts to decrease gastric acid secretion, which reduces stomach acidity. Pantoprazole administration leads to long-lasting inhibition of gastric acid secretion. **General Effects** Pantoprazole has been shown to reduce acid reflux-related symptoms, heal inflammation of the esophagus, and improve patient quality of life more effectively than histamine-2 receptor antagonists (H2 blockers). This drug has an excellent safety profile and a low incidence of drug interactions. It can be used safely in various high-risk patient populations, including the elderly and those with renal failure or moderate hepatic dysfunction. Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as pantoprazole have been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal _C. difficile_), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life. PPIs such as pantoprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes. **A note on laboratory testing abnormalities** During treatment with antisecretory medicinal products such as pantoprazole, serum gastrin (a peptide hormone that stimulates secretion of gastric acid) increases in response to the decreased acid secretion caused by proton pump inhibition. The increased gastrin level may interfere with investigations for neuroend

Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump, expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid). Proton pump inhibitors such as pantoprazole are substituted _benzimidazole_ derivatives, weak bases, which accumulate in the acidic space of the parietal cell before being converted in the _canaliculi_ (small canal) of the gastric parietal cell, an acidic environment, to active _sulfenamide_ derivatives. This active form then makes disulfide bonds with important cysteines on the gastric acid pump, inhibiting its function. Specifically, pantoprazole binds to the _sulfhydryl group_ of H+, K+-ATPase, which is an enzyme implicated in accelerating the final step in the acid secretion pathway. The enzyme is inactivated, inhibiting gastric acid secretion. The inhibition of gastric acid secretion is stronger with proton pump inhibitors such as pantoprazole and lasts longer than with the H(2) antagonists.

Pantoprazole is a proton pump inhibitor. It accumulates in the acidic compartment of parietal cells and is converted to the active form, a sulfanilamide, which binds to hydrogen-potassium-ATP-ase at the secretory surface of gastric parietal cells. Inhibition of hydrogen-potassium-ATPase blocks the final step of gastric acid production, leading to inhibition of both basal and stimulated acid secretion. The duration of inhibition of acid secretion does not correlate with the much shorter elimination half-life of pantoprazole. /Pantoprazole sodium/

About 1 hour

Elimination: Following oral or intravenous administration: 1 hour. The half-life of pantoprazole is prolonged (7 to 9 hours) in patients with cirrhosis of the liver and in genetically determined slow metabolizers (3.5 to 10 hours). /Pantoprazole sodium/

Pantoprazole is heavily metabolized in the liver by the cytochrome P450 (CYP) system. Pantoprazole metabolism is independent of the route of administration (intravenous or oral). The main metabolic pathway is _demethylation_, by _CYP2C19_ hepatic cytochrome enzyme, followed by sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites are pharmacologically active. After hepatic metabolism, almost 80% of an oral or intravenous dose is excreted as metabolites in urine; the remainder is found in feces and originates from biliary secretion.

Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system. Pantoprazole metabolism is independant of route of administration (intravenous or oral). The main metabolic pathway is demethylation,by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. ... CYP2C19 displays a known genetic polymorphism due to its deficiency in some sub-populations (eg 3% of Caucasians and African-Americans and 17 to 23% of Asians). /Pantoprazole sodium/

D8TST4O562

PANTOPRAZOLE

Established Pharmacologic Class [EPC] - Proton Pump Inhibitor

Mechanisms of Action [MoA] - Proton Pump Inhibitors

Pantoprazole is a Proton Pump Inhibitor. The mechanism of action of pantoprazole is as a Proton Pump Inhibitor.

PANTOPRAZOLE

Various agents with different action mechanisms used to treat or ameliorate PEPTIC ULCER or irritation of the gastrointestinal tract. This has included ANTIBIOTICS to treat HELICOBACTER INFECTIONS; HISTAMINE H2 ANTAGONISTS to reduce GASTRIC ACID secretion; and ANTACIDS for symptomatic relief.

Compounds that inhibit H(+)-K(+)-EXCHANGING ATPASE. They are used as ANTI-ULCER AGENTS and sometimes in place of HISTAMINE H2 ANTAGONISTS for GASTROESOPHAGEAL REFLUX.

Pantoprazole is absorbed after oral administration as an enteric-coated tablet with maximum plasma concentrations attained within 2 – 3 hours and a bioavailability of 77% that does not change with multiple dosing. Following an oral dose of 40mg, the Cmax is approximately 2.5 μg/mL with a tmax of 2 to 3 hours. The AUC is approximately 5 μg.h/mL. There is no food effect on AUC (bioavailability) and Cmax. Delayed-release tablets are prepared as enteric-coated tablets so that absorption of pantoprazole begins only after the tablet leaves the stomach.

After a single oral or intravenous (IV) dose of 14C-labeled pantoprazole to healthy, normal metabolizing subjects, about 71% of the dose was excreted in the urine, with 18% excreted in the feces by biliary excretion. There was no kidney excretion of unchanged pantoprazole.

The apparent volume of distribution of pantoprazole is approximately 11.0-23.6 L, distributing mainly in the extracellular fluid.

**Adults**: With intravenous administration of pantoprazole to extensive metabolizers, total clearance is 7.6-14.0 L/h. In a population pharmacokinetic analysis, the total clearance increased with increasing body weight in a non-linear fashion. **Children**: clearance values in the children 1 to 5 years old with endoscopically proven GERD had a median value of 2.4 L/h.

Time to peak concentration: Following an oral dose of 40 mg in extensive metabolizers with normal hepatic function: 2.4 hours. When pantoprazole is taken with food, the time to peak concentration is variable and may be significantly increased. /Pantoprazole sodium/

Peak serum concentration: Following an oral dose of 40 mg in extensive metabolizers with normal hepatic function: 2.4 ug/mL. Following an intravenous dose of 40 mg administered over 15 minutes to extensive metabolizers with normal hepatic function: 5.51 ug/mL. /Pantoprazole sodium/

Medication: Antiulcerative

Use (kg; approx.) in Germany (2009): >10000；Use (kg; exact) in Germany (2009): 20548；Use (kg) in USA (2002): 8200；Use (kg) in France (2004): 5287；Consumption (g per capita; approx.) in Germany (2009): 0.122；Consumption (g per capita; exact) in Germany (2009): 0.251；Consumption (g per capita) in the USA (2002): 0.0291；Consumption (g per capita) in France (2004): 0.0875；Excretion rate: 0.06；Calculated removal (%): 9.8

Pantoprazole is available as enteric coated tablets containing 45.1 mg of the sodium salt sesquihydrate equivalent to 40 mg ... of the free anhydrous acid, and as a lyophylisate for iv infusion.

Trade name: Protonix

Preparation: B. Kohl et al, EP 166287; eidem, US 4758579 (1986, 1988 both to Byk Gluden)

Information available in 2004 indicated that Pantoprazole was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Argentina, Bahrain, Brazil, Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, India, Iraq, Israel, Jordan, Lebanon, Libyan Arab Jamahiriya, Luxembourg, Malaysia, Mexico, Nicaragua, Nigeria, Oman, Panama, Poland, Portugal, Romania, Saudi Arabia, Singapore, Somalia, South Africa, Sudan, Thailand, Tunisia, United Arab Emirates, Yemen (1,2)

Information available in 2004 indicated that Pantoprazole sodium was used in the manufacture of pharmaceutical preparations in the following countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Ecuador, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Indonesia, Ireland, Italy, Luxembourg, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, USA, Yugoslavia (1,2) /Pantoprazole sodium/